Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.

Summary

Is aging ineluctable, or are there genetic programs of aging that could be manipulated to extend life span? Research over the past two decades has provided powerful evidence that aging is indeed regulated by genes that control highly conserved pathways (1). For example, mutations in single genes in model organisms like flies and worms not only allow these animals to live longer, but rejuvenate them as well (2). Even the single-celled budding yeast Saccharomyces cerevisiae ages, and specific genes likewise control this process (1). Indeed, one of the most powerful genetic manipulations to extend life span was discovered in yeast. The histone deacetylase silent information regulator 2 (Sir2) is required for repressing the transcription of certain mating-type loci, telomeres, and ribosomal DNA (3–5). The latter had been linked to aging in yeast, inspiring studies that revealed Sir2's importance for this process (6). Subsequent work in yeast and animal models established that changes in Sir2 activity are responsible for much of the life span–extending effects of caloric restriction (7). On page 1184 of this issue, Schlissel et al. (8) report that a particular facet of aging, which had long been attributed to age-dependent changes in Sir2 function, is caused by a new mechanism.